Influenza A virus (IAV) infection is one of the most important causes of respiratory tract diseases and is responsible for widespread morbidity and mortality. During the first several days after infection, the host develops a complex and effective innate immune response that allows to contain IAV replication pending the development of adaptive immune responses. However, at later time points, increased susceptibility to bacterial superinfection can occur leading to mortality during IAV epidemics and pandemics. For instance bacterial pneumonias accounted for the majority of deaths (˜50 million deaths worldwide) in the 1918 pandemic (Spanish flu). Among the predominant bacteria species causing bacterial superinfection post-IAV are Streptococcus pneumoniae (the pneumococcus), Haemophilus influenzae and Staphylococcus aureus. Thus, there is a need for treatment of bacterial superinfections post-influenza. Although there are evidences of specific features of individual types of bacteria, the mechanisms leading to enhance susceptibility to secondary bacterial infection seem to be broad-based and include alterations of mechanical and immunological defences. Indeed, alteration of the physical barriers to bacterial adhesion and invasion including alteration of the mucosa as well as the exposition of new attachment sites for the bacteria have been described. In parallel, impairment of the host innate (rather than adaptive) response is a cardinal feature of bacterial-associated pneumonia post-influenza challenge. There are now strong evidences that TLRS signaling induces protective mechanisms against bacterial infections. For instance, it was also showed that mucosal administration of flagellin into mice could protect against Streptococcus pneumoniae lung infection. The anti-infectious properties of flagellin were mainly observed when the TLRS ligand was co-administrated with the pathogen or 2 to 24 h before the bacterial challenge (Munoz N, Van Maele L, Marques J M, Rial A, Sirard J C, Chabalgoity J A. Mucosal administration of flagellin protects mice from Streptococcus pneumoniae lung infection. Infect Immun 2010; 78:4226-33).